Article
- The EMBO Journal (2004) 23, 3701 - 3710
- doi:10.1038/sj.emboj.7600378
Published online: 9 September 2004
Subject Categories:
Two WXXF-based motifs in NECAPs define the specificity of accessory protein binding to AP-1 and AP-2
Brigitte Ritter1, Alexei Yu Denisov2, Jacynthe Philie1, Christophe Deprez2, Elaine C Tung1, Kalle Gehring2 and Peter S McPherson1
- Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, QC, Canada
- Department of Biochemistry and Montreal Joint Centre for Structural Biology, McGill University, Montreal, QC, Canada
Correspondence to:
Peter S McPherson, CBET Group, Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, 3801 University St., Montreal, Quebec, Canada, H3A 2B4. Tel.: +1 514 398 7355; Fax: +1 514 398 8106; E-mail: peter.mcpherson@mcgill.ca
Received 2 April 2004; Accepted 29 July 2004
Abstract
The adaptor proteins AP-2 and AP-1/GGAs are essential components of clathrin coats at the plasma membrane and trans-Golgi network, respectively. The adaptors recruit accessory proteins to clathrin-coated pits, which is dependent on the adaptor ear domains engaging short peptide motifs in the accessory proteins. Here, we perform an extensive mutational analysis of a novel WXXF-based motif that functions to mediate the binding of an array of accessory proteins to the 
-adaptin ear domain of AP-2. Using nuclear magnetic resonance and mutational studies, we identified WXXF-based motifs as major ligands for a site on the -ear previously shown to bind the DPW-bearing proteins epsin 1/2. We also defined the determinants that allow for specific binding of the -ear motif to AP-2 as compared to those that allow a highly related WXXF-based motif to bind to the ear domains of AP-1/GGAs. Intriguingly, placement of acidic residues around the WXXF cores is critical for binding specificity. These studies provide a structural basis for the specific recruitment of accessory proteins to appropriate sites of clathrin-coated vesicle formation.
Keywords:
- AAK1,
- clathrin,
- endocytosis,
- stonin,
- synaptojanin
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